NSAIDs Flashcards
1
Q
What are the free key examples of NSAIDs
A
- aspirin
- ibuprofen
- paracetamol (not strictly)
2
Q
How is prostaglandin produced?
A
- Phospholipid is converted into arachidonic acid using phospholipase A2
- Arachidonic acid is converted into prostaglandins by cyclooxygenase
3
Q
What do NSAIDs inhibit?
A
cyclooxyrgenase
4
Q
What are the three effects of NSAIDs?
A
- analgesia (prevent prostaglandin synthesis, prostaglandins sensitive nerve endings)
- anti-inflammatory (local inflammation controlled by preventing PG synthesis)
- anti-pyeretic (able to reduce a raised body temp). (blocks PG synthesis)
5
Q
What is the mechanism of action?
A
- irreversible inhibition of cyclooxyrgenase (aspirin)
- reversible inhibition of COX (ibuprofen)
- Reversible non-competitive inhibition of COX (paracetamol)
6
Q
Why is paracetamol kinder on the stomach in comparison to aspirin?
A
slides
7
Q
What is COX1 and what is its role?
A
- constitutive enzyme
- ubiquitously expressed
- responsible for gut effects
8
Q
How is COX2 expressed?
A
induced expression at sites of inflammation
9
Q
What is COX2 responsible for?
A
inflammation
10
Q
Why is paracetamol potentially dangerous?
A
- because slightly higher doses can be lethal.
- if you overdose on paracetamol, has a high Km (high cones to engage P459 system) which generates a toxic metabolite this will destroy liver cells.
- at a low dose this metabolism pathway does not occur
11
Q
How do you treat a paracetamol overdose?
A
- use a calibration curve to determine risk
- measure conc of paracetamol in the blood
- need glutathione (use acetylcysteine or methionine to increase levels)
12
Q
What are the risks of overdose treatment?
A
-if you are a smoker or a drinker you metabolise paracetamol faster (produce more toxic metabolite for a lower conc of paracetamol in the blood)
